Properties of the hyperpolarizing‐activated current (if) in cells isolated from the rabbit sino‐atrial node.

Abstract

SUMMARY1. Individual cells were isolated from the sino-atrial node area of the rabbit heart using an enzyme medium containing collagenase and elastase. After enzymatic treatment the cells were placed in normal Tyrode solution, where beating resumed in a fraction of them.2. Isolated cells were studied in the whole cell configuration. Action potentials as well as membrane currents under voltage-clamp conditions were similar to those in multicellular preparations.3. Pulses to voltages more negative than about -50 mV caused activation of the hyperpolarizing-activated current, if. Investigation of the properties of this current was carried out under conditions that limited the influence of other current systems during voltage clamp.4. The if current activation range usually extended approximately from -50 to -100 mV, but varied from cell to cell. In several cases, pulsing to the region of -40 mV elicited a sizeable if. Both current activation and deactivation during voltage steps had S-shaped time courses. A high variability was however observed in the sigmoidal behaviour of if kinetics. 5. Plots of the fully-activated current-voltage (I-V) relation in different extracellular Na and K concentrations showed that both ions carry the current if. While changes in the external Na concentration caused the current I-V relation to undergo simple shifts along the voltage axis, changes in extracellular K concentration were also associated with changes in its slope. Again, a large variability was observed in the increase of I-V slope on raising the external K concentration.6. The current if was strongly depressed by Cs, and the block induced by 5 mM-Cs was markedly voltage dependent.

Normal Heart Rhythm is Initiated and Regulated by an Intracellular Calcium Clock Within Pacemaker Cells

“…8B and 10); but this does not involve I f , because this current is cAMP-(but not PKA-) dependent [31,32]. As discussed above, β-AR stimulation of SANC beating rate is markedly blunted in the presence of ryanodine, indicating a minor role of the membrane clock (including I f ) in the rate regulation following βAR stimulation [5].…”

Isolation, Characterization and Differentiation Potential of Cardiac Progenitor Cells in Adult Pigs

“…The sinuatrial node function thanks to the presence of specific channels, called HCN channels (Hyperpolarization-activated cyclic nucleotide-gated), through which passes an inward current of potassium ions (K + ) able to induce depolarization (Di Francesco et al 1986). The intensity and frequency of the inward current is governed by the hyperpolarization potential and by the intracellular concentration of cAMP.…”

Developmental changes in functional expression and β-adrenergic regulation of If in the heart of mouse embryo

“…It is well know that If increases in response to ISO in adult cardiomyocytes [1], [21]. We testedadrenergic regulation of If at -110 mV.…”

“…The hyperpolarization-activated current (I ƒ ) is a nonselective inward current activated on hyperpolarization during the diastolic depolarization period of action potential in heart sino-atrial node and Purkinje system, and plays an important role in the generation and regulation of pacemaker activity in both primary and secondary pacemaker cells [1][2][3]. The biophysical characteristics of I ƒ comprise timedependent activation kinetics, a linear current-voltage (I-V) relationship and voltage-dependent block upon extracellular application of Cs + .…”

“…It has been well documented that both sympathetic and parasympathetic control of heart rate involves modulation of I ƒ [4]. In adult mammalian heart, -adrenergic agonist isoproterenol (ISO) stimulates I ƒ by shifting the activation curve to more positive potentials [1], whereas the vagal neurotransmitter acetycholine (ACh) inhibits I ƒ by shifting the activation curve to more negative potentials [5]. This control is exerted through modulation of adenylate cyclase (AC) and cAMP [6].…”